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https://www.readbyqxmd.com/read/28427827/antiviral-screen-identifies-ev71-inhibitors-and-reveals-camptothecin-target-dna-topoisomerase-1-as-a-novel-ev71-host-factor
#1
Kan Xing Wu, Justin Jang-Hann Chu
Enterovirus 71 (EV71) is one of the causative agents of hand, foot and mouth disease (HFMD) associated with severe neurological disease. EV71's pathogenesis remains poorly understood and the lack of approved antiviral has led to its emergence as a clinically important neurotropic virus. The goals of this study were to: (i) identify novel anti-EV71 compounds that may serve as lead molecules for therapeutics; and (ii) investigate their targets in downstream studies. We screened a 502-compound library of highly purified natural products for anti-EV71 activities in a cell-based immunofluorescence assay that were then confirmed in viral plaque reduction assays...
April 17, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28424289/disruption-of-mda5-mediated-innate-immune-responses-by-the-3c-proteins-of-coxsackievirus-a16-coxsackievirus-a6-and-enterovirus-d68
#2
Yajuan Rui, Jiaming Su, Hong Wang, Junliang Chang, Shaohua Wang, Wenwen Zheng, Yong Cai, Wei Wei, James T Gordy, Richard Markham, Wei Kong, Wenyan Zhang, Xiao-Fang Yu
Coxsackievirus A16 (CV-A16), A6 (CV-A6), and enterovirus D68 (EV-D68) belong to the Picornaviridae family and are major causes of hand, foot, and mouth disease (HFMD) and pediatric respiratory disease worldwide. The biological characteristics of these viruses, especially their interplay with the host innate immune system, have not been well investigated. In this study, we discovered that the 3C(pro) proteins from CV-A16, CV-A6, and EV-D68 bind MDA5 and inhibit its interaction with MAVS. Consequently, MDA5-triggered type I IFN signaling in the RLR pathway was blocked by CV-A16, CV-A6, and EV-D68 3C(pro) Furthermore, CV-A16, CV-A6, and EV-D68 3C(pro) all cleave TAK1, resulting in inhibition of NF-κB activation, a host response also critical for toll-like receptor (TLR) mediated signaling...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28424287/protective-efficacy-of-formaldehyde-inactivated-whole-virus-vaccine-and-antivirals-in-a-murine-model-of-coxsackievirus-a10-infection
#3
Zhenjie Zhang, Zhaopeng Dong, Juan Li, Michael J Carr, Dongming Zhuang, Jianxing Wang, Yawei Zhang, Shujun Ding, Yigang Tong, Dong Li, Weifeng Shi
Coxsackievirus A10 (CVA10) is one of the major pathogens associated with hand, foot and mouth disease (HFMD). CVA10 infection can cause herpangina and viral pneumonia, which can be complicated by severe neurological sequelae. Morbidity and mortality of CVA10-associated HFMD has been increasing in recent years, particularly in the pan-Pacific region. There are limited studies however on the pathogenesis and immunology of CVA10-associated HFMD infections, and few antiviral drugs or vaccines have been reported...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28422137/effective-in-vivo-therapeutic-igg-antibody-against-vp3-of-enterovirus-71-with-receptor-competing-activity
#4
Qiang Jia, Qingyong Ng, Wenjie Chin, Tao Meng, Vincent Tak Kwong Chow, Cheng-I Wang, Jimmy Kwang, Fang He
Passive immunization is an effective option for treatment against hand, foot and mouth disease caused by EV71, especially with cross-neutralizing IgG monoclonal antibodies. In this study, an EV71-specific IgG2a antibody designated 5H7 was identified and characterized. 5H7 efficiently neutralizes the major EV71 genogroups (A, B4, C2, C4). The conformational epitope of 5H7 was mapped to the highly conserved amino acid position 74 on VP3 capsid protein using escape mutants. Neutralization with 5H7 is mediated by the inhibition of viral attachment, as revealed by virus-binding and post-attachment assays...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28422128/epidemiology-of-45-616-suspect-cases-of-hand-foot-and-mouth-disease-in-chongqing-china-2011-2015
#5
Jian Tao, Xiao-Yan He, Yu Shi, Guohun Zhu, Shan Liu, Zhenzhen Zhang, Shi Tang, Rong Zhang, Bin Peng, Zhidai Liu, Junjie Tan, Qian Chen, Xingbin Wang, Liming Bao, Lin Zou, Penghui Zhang
Epidemiology and etiology of hand, foot, and mouth disease (HFMD) based on large sample size or evaluation of detection for more enterovirus serotypes are not well investigated in Chongqing of China. 45,616 suspect HFMD patients were prospectively enrolled among whom 21,615 were laboratory confirmed HFMD cases over a 5-year period (January 2011 to December 2015). Their epidemiological, clinical, and laboratory data were extracted and stratified by month, age, sex, disease severity, and enterovirus serotype...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28414218/exploiting-the-anti-aggregation-of-gold-nanostars-for-rapid-detection-of-hand-foot-and-mouth-disease-causing-enterovirus-71-using-surface-enhanced-raman-spectroscopy
#6
Miguel Reyes, Marek Piotrowski, Swee Kim Ang, Jingqi Chan, Shuai He, Justin Jang Hann Chu, James Chen Yong Kah
Enterovirus 71 (EV71) is a major public health threat that requires rapid point-of-care detection. Here, we developed a surface-enhanced Raman spectroscopy (SERS)-based scheme that utilized protein-induced aggregation of colloidal gold nanostars (AuNS) to rapidly detect EV71 without the need for fabricating a solid substrate, Raman labels or complicated sample handling. We used AuNS (hydrodynamic diameter, DH of 105.12 ± 1.13 nm) conjugated to recombinant scavenger receptor class B, member 2 (SCARB2) protein with known affinity to EV71...
April 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28413485/therapeutic-efficacy-of-phentolamine-in-the-management-of-severe-hand-foot-and-mouth-disease-combined-with-pulmonary-edema
#7
Zhixin Yan, Yaokai Shang, Fengxian Li, Fei Xie, Huili Qian, Youqi Zhang, Bin Yue
The aim of this study was to examine the effects of phentolamine on severe hand, foot and mouth disease (HFMD) combined with pulmonary edema (PE). From May 2008 to December 2012, 53 children with severe HFMD plus PE were enrolled in the treatment group, receiving phentolamine intravenously at a loading dose of 5 µg/kg/min. The control group comprised 52 children with the same disease who did not receive phentolamine infusion. Data concerning creatine kinase (CK), CK-MB, cardiac troponin I (cTnI), heart rate, systolic blood pressure (SBP) and the duration of ventilation dependence and hospitalization were collected...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28412679/epidemic-characteristics-of-main-infectious-diseases-in-yantai-city-between-2010-and-2012-and-prevention-strategy-research
#8
Huimin Gao, Wenbo Luan, Maobo Wang, Yanjie Dong
To investigate the epidemic characteristics and prevention strategies of main infectious diseases. From 2010 to 2012, 23 notifiable diseases were reported in Yantai with average reported cases of 17,376. The morbidity was the highest in 2012 and the lowest in 2011. The accumulated death toll was 101 with the highest death rate in 2011 and the lowest in 2012. Major class A and B infectious diseases included viral hepatitis, phthisis, syphilis, clap and dysentery. The major class C infectious disease was hand-foot-and-mouth disease every year...
November 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28412182/characterization-of-three-small-molecule-inhibitors-of-enterovirus-71-identified-from-screening-of-a-library-of-natural-products
#9
Guiming Li, Qianqian Gao, Shilin Yuan, Lili Wang, Ralf Altmeyer, Ke Lan, Feifei Yin, Gang Zou
Enterovirus 71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD). Infection with EV-A71 is more often associated with neurological complications in children and is responsible for the majority of fatalities, but currently there is no approved antiviral therapy for treatment. Here, we identified auraptene, formononetin, and yangonin as effective inhibitors of EV-A71 infection in the low-micromolar range from screening of a natural product library. Among them, formononetin and yangonin selectively inhibited EV-A71 while auraptene could inhibit viruses within the enterovirus species A...
April 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28412150/epidemiological-features-of-and-changes-in-incidence-of-infectious-diseases-in-china-in-the-first-decade-after-the-sars-outbreak-an-observational-trend-study
#10
Shigui Yang, Jie Wu, Cheng Ding, Yuanxia Cui, Yuqing Zhou, Yiping Li, Min Deng, Chencheng Wang, Kaijin Xu, Jingjing Ren, Bing Ruan, Lanjuan Li
BACKGROUND: The model of infectious disease prevention and control changed significantly in China after the outbreak in 2003 of severe acute respiratory syndrome (SARS), but trends and epidemiological features of infectious diseases are rarely studied. In this study, we aimed to assess specific incidence and mortality trends of 45 notifiable infectious diseases from 2004 to 2013 in China and to investigate the overall effectiveness of current prevention and control strategies. METHODS: Incidence and mortality data for 45 notifiable infectious diseases were extracted from a WChinese public health science data centre from 2004 to 2013, which covers 31 provinces in mainland China...
April 12, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28408118/a-novel-combined-vaccine-based-on-monochimeric-vlp-co-displaying-multiple-conserved-epitopes-against-enterovirus-71-and-varicella-zoster-virus
#11
Yangtao Wu, Rui Zhu, Longfa Xu, Yongchao Li, Shuxuan Li, Hai Yu, Shaowei Li, Hua Zhu, Tong Cheng, Ningshao Xia
Chicken pox and hand, foot and mouth disease (HFMD) are two major infectious diseases that mainly affect infants and children, causing significant morbidity annually. Varicella-zoster virus (VZV) and enterovirus 71 (EV71), respectively, are the principal epidemic pathogens causing these two diseases. To investigate the possibility of developing a novel combined vaccine to prevent chicken pox and HFMD, we constructed three chimeric virus-like particles (VLPs) (termed HBc-V/1/2, HBc-2/V/1 and HBc-1/2/V) based on the hepatitis B core antigen (HBc) carrier that display epitopes derived from VZV-gE, EV71-VP1, and EV71-VP2 in a varied tandem manner...
April 10, 2017: Vaccine
https://www.readbyqxmd.com/read/28406470/spatio-temporal-pattern-and-risk-factor-analysis-of-hand-foot-and-mouth-disease-associated-with-under-five-morbidity-in-the-beijing-tianjin-hebei-region-of-china
#12
https://www.readbyqxmd.com/read/28399485/interleukin-18-protects-mice-from-enterovirus-71-infection
#13
Zheng Li, Hongbin Wang, Yihui Chen, Junling Niu, Qiuhong Guo, Qibin Leng, Zhong Huang, Zhirui Deng, Guangxun Meng
Previous study has demonstrated that the NLRP3 inflammasome is essential for protecting murine host against Enterovirus 71 (EV71) infection. However, the underlying mechanism remained unknown. Here we discovered that the pleiotropic cytokine interleukin-18 (IL-18), an NLRP3 inflammasome-dependent effector protein, exhibits a protective capability against EV71 challenge. Deficiency of IL-18 in mice exacerbated EV71 infection, which was reflected by increased viral replication, elevated production of interferons (IFN-β, IFN-γ), proinflammatory cytokines (TNF-α, IL-6) and chemokine CCL2,as well as decreased survival of experimental animals...
April 8, 2017: Cytokine
https://www.readbyqxmd.com/read/28384566/impact-of-genetic-changes-pathogenicity-and-antigenicity-on-enterovirus-a71-vaccine-development
#14
REVIEW
Pinn Tsin Isabel Yee, Chit Laa Poh
Enterovirus-A71 (EV-A71) is an etiological agent of the hand, foot and mouth disease (HFMD). EV-A71 infection produces high fever and ulcers in children. Some EV-A71 strains produce severe infections leading to pulmonary edema and death. Although the protective efficacy of the inactivated vaccine (IV) was ≥90% against mild HFMD, there was approximately 80% protection against severe HFMD. The monovalent EV-A71 IV elicits humoral immunity but lacks long-term immunogenicity. Spontaneous mutations of the EV-A71 genome could lead to antigenicity changes and the virus may not be neutralized by antibodies elicited by the IV...
April 3, 2017: Virology
https://www.readbyqxmd.com/read/28367766/epidemics-and-aetiology-of-hand-foot-and-mouth-disease-in-xiamen-china-from-2008-to-2015
#15
S Z He, M Y Chen, X R Xu, Q Yan, J J Niu, W H Wu, X S Su, S X Ge, S Y Zhang, N S Xia
Over the past 8 years, human enteroviruses (HEVs) have caused 27 227 cases of hand, foot and mouth disease (HFMD) in Xiamen, including 99 severe cases and six deaths. We aimed to explore the molecular epidemiology of HFMD in Xiamen to inform the development of diagnostic assays, vaccines and other interventions. From January 2009 to September 2015, 5866 samples from sentinel hospitals were tested using nested reverse transcription PCR that targeted the HEV 5' untranslated region and viral protein 1 region. Of these samples, 4290 were tested positive for HEV and the amplicons were sequenced and genotyped...
April 3, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28351680/human-lung-fibroblast-derived-matrix-facilitates-vascular-morphogenesis-in-3d-environment-and-enhances-skin-wound-healing
#16
Ping Du, Muhammad Suhaeri, Sang Su Ha, Seung Ja Oh, Sang Heon Kim, Kwideok Park
Extracellular matrix (ECM) is crucial to many aspects of vascular morphogenesis and maintenance of vasculature function. Currently the recapitulation of angiogenic ECM microenvironment is still challenging, due mainly to its diverse components and complex organization. Here we investigate the angiogenic potential of human lung fibroblast-derived matrix (hFDM) in creating a three-dimensional (3D) vascular construct. hFDM was obtained via decellularization of in vitro cultured human lung fibroblasts and analyzed via immunofluorescence staining and ELISA, which detect multiple ECM macromolecules and angiogenic growth factors (GFs)...
March 25, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28322333/squamous-epitheliotropism-of-enterovirus-a71-in-human-epidermis-and-oral-mucosa
#17
Win Kyaw Phyu, Kien Chai Ong, Chee Kwan Kong, Abdul Khalil Alizan, Tindivanam Muthurangam Ramanujam, Kum Thong Wong
Hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by Enterovirus A71 (Genus: Enterovirus, Family: Picornaviridae). Typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. Although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of Enterovirus A71 in human skin and oral mucosa are unknown. In Enterovirus A71-infected human skin and oral mucosa organotypic cultures derived from the prepuce and lip biopsies, focal viral antigens and viral RNA were localized to cytoplasm of epidermal and mucosal squamous cells as early as 2 days post-infection...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302925/best-practices-to-prevent-transmission-and-control-outbreaks-of-hand-foot-and-mouth-disease-in-childcare-facilities-a-systematic-review
#18
REVIEW
J Hy Chan, C K Law, E Hamblion, H Fung, J Rudge
INTRODUCTION: Hand, foot, and mouth disease continues to cause seasonal epidemics in the Asia-Pacific Region. Since the current Enterovirus 71 vaccines do not provide cross-protection for all Enterovirus species that cause hand, foot, and mouth disease, there is an urgent need to identify appropriate detection tools and best practice to prevent its transmission and to effectively control its outbreaks. This systematic review aimed to identify characteristics of outbreak and assess the impact and effectiveness of detection tools and public health preventive measures to interrupt transmission...
March 17, 2017: Hong Kong Medical Journal, Xianggang Yi Xue za Zhi
https://www.readbyqxmd.com/read/28274636/enhancing-enterovirus-a71-vaccine-production-yield-by-microcarrier-profusion-bioreactor-culture
#19
Chia-Chyi Liu, Suh-Chin Wu, Shang-Rung Wu, Hsiao-Yu Lin, Meng-Shin Guo, Alan Yung-Chih Hu, Yen-Hung Chow, Jen-Ron Chiang, Dar-Bin Shieh, Pele Chong
Hand, foot and mouth diseases (HFMD) are mainly caused by Enterovirus A71 (EV-A71) infections. Clinical trials in Asia conducted with formalin-inactivated EV-A71 vaccine candidates produced from serum-free Vero cell culture using either roller bottle or cell factory technology, are found to be safe and highly efficacious. To increase vaccine yields and reduce the production costs, the bioprocess improvement for EV-A71 vaccine manufacturing is currently being investigated. The parameters that could affect and enhance the production yields of EV-A71 virus growth in the microcarrier bioreactor were investigated...
March 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28250116/a-neonatal-murine-model-of-coxsackievirus-a6-infection-for-evaluation-of-antiviral-and-vaccine-efficacy
#20
Zhenjie Zhang, Zhaopeng Dong, Qingjuan Wei, Michael J Carr, Juan Li, Shujun Ding, Yigang Tong, Dong Li, Weifeng Shi
Hand, foot and mouth disease (HFMD) is a global health concern. Family Picornaviridae members, particularly enterovirus 71 (EVA71) and Coxsackievirus A16 (CVA16), are the primary etiological agents of HFMD, however, a third enterovirus A species, CoxsackievirusA6 (CVA6), has been recently associated with epidemic outbreaks. Study of the pathogenesis of CVA6 infection and development of antivirals and vaccines are hindered due to the lack of appropriate animal models. We have developed and characterized a murine model of CVA6 infection which was employed to evaluate the antiviral activities of different drugs and the protective efficacies of CVA6-inactivated vaccines...
March 1, 2017: Journal of Virology
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